Birth characteristics and childhood leukemia in Switzerland: a register-based case-control study.

PURPOSE Initial genetic alterations in the development of childhood leukemia occur in utero or before conception; both genetic and environmental factors are suspected to play a role. We aimed to investigate the associations between childhood leukemia and perinatal characteristics including birth order, birth interval to older siblings, parental age, birth weight, and multiple birth. METHODS We identified cases diagnosed between 1981 and 2015 and born in Switzerland between 1969 and 2015 from the Swiss Childhood Cancer Registry and randomly sampled five controls per case from national birth records matched on date of birth, sex, and municipality of residence at birth. We used conditional logistic regression to investigate associations between perinatal characteristics and leukemia at ages 0-15 and 0-4 years, and the subtypes acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS The study included 1,403 cases of leukemia. We observed increased risks associated with high birth weight (adjusted OR 1.37, 95% CI 1.12-1.69) and multiple birth (1.89, 1.24-2.86). These associations were similar for ALL and stronger for leukemia at ages 0-4 years. For AML, we observed an increased risk for higher birth order (3.08, 0.43-22.03 for fourth or later born children). We found no associations with other perinatal characteristics. CONCLUSION This register-based case-control study adds to the existing evidence of a positive association between high birth weight and risk of childhood leukemia. Furthermore, it suggests children from multiple births are at an increased risk of leukemia

Space-time clustering of childhood cancers: a systematic review and pooled analysis.

The aetiology of childhood cancers remains largely unknown. Space-time clustering of cases might imply an aetiological role of infections. We aimed to review the evidence of space-time clustering of specific childhood cancers. We searched Medline and Embase for population-based studies that covered a pre-defined study area, included cases under 20 years of age and were published before July 2016. We extracted all space-time clustering tests and calculated the proportion of positive tests per diagnostic group. In a pooled analysis, we performed a Knox test of the number of pairs of cases close to each other in time and space pooled across studies. 70 studies met our eligibility criteria, 32 of which reported Knox tests. For leukaemia, the proportion of positive tests was higher than expected by chance at both time of diagnosis (26%) and birth (11%). The pooled analysis showed strong evidence of clustering at diagnosis for children aged 0-5 years for a spatial and temporal lag of 5 km and 6 months, respectively (p < 0.001). The evidence was mixed for lymphoma and tumours of the central nervous system. The current study suggests that leukaemia cases cluster in space-time due to an aetiological factor affecting children under 5 years of age. The observed pattern of clustering of young children close to time of diagnosis is compatible with Greaves' delayed-infections-hypothesis

Space-Time Clustering of Childhood Leukemia: Evidence of an Association with ETV6-RUNX1 (TEL-AML1) Fusion

BACKGROUND: Many studies have observed space-time clustering of childhood leukemia (CL) yet few have attempted to elicit etiological clues from such clustering. We recently reported space-time clustering of CL around birth, and now aim to generate etiological hypotheses by comparing clustered and nonclustered cases. We also investigated whether the clustering resulted from many small aggregations of cases or from a few larger clusters. METHODS: We identified cases of persons born and diagnosed between 1985 and 2014 at age 0-15 years from the Swiss Childhood Cancer Registry. We determined spatial and temporal lags that maximized evidence of clustering based on the Knox test and classified cases born within these lags from another case as clustered. Using logistic regression adjusted for child population density, we determined whether clustering status was associated with age at diagnosis, immunophenotype, cytogenetic subtype, perinatal and socioeconomic characteristics, and pollution sources. RESULTS: Analyses included 1,282 cases of which 242 were clustered (born within 1 km and 2 years from another case). Of all investigated characteristics only the t(12;21)(p13;q22) translocation (resulting in ETV6-RUNX1 fusion) differed significantly in prevalence between clustered and nonclustered cases (40% and 25%, respectively; adjusted OR 2.54 [1.52-4.23]; p = 0.003). Spatio-temporal clustering was driven by an excess of aggregations of two or three children rather than by a few large clusters. CONCLUSION: Our findings suggest ETV6-RUNX1 is associated with space-time clustering of CL and are consistent with an infection interacting with that oncogene in early life leading to clinical leukemia

Population mixing and the risk of childhood leukaemia in Switzerland: a census-based cohort study

Childhood leukaemia (CL) may have an infectious cause and population mixing may therefore increase the risk of CL. We aimed to determine whether CL was associated with population mixing in Switzerland. We followed children aged <16 years in the Swiss National Cohort 1990-2008 and linked CL cases from the Swiss Childhood Cancer Registry to the cohort. We calculated adjusted hazard ratios (HRs) for all CL, CL at age <5 years and acute lymphoblastic leukaemia (ALL) for three measures of population mixing (population growth, in-migration and diversity of origin), stratified by degree of urbanisation. Measures of population mixing were calculated for all municipalities for the 5-year period preceding the 1990 and 2000 censuses. Analyses were based on 2,128,012 children of whom 536 developed CL. HRs comparing highest with lowest quintile of population growth were 1.11 [95 % confidence interval (CI) 0.65-1.89] in rural and 0.59 (95 % CI 0.43-0.81) in urban municipalities (interaction: p = 0.271). Results were similar for ALL and for CL at age <5 years. For level of in-migration there was evidence of a negative association with ALL. HRs comparing highest with lowest quintile were 0.60 (95 % CI 0.41-0.87) in urban and 0.61 (95 % CI 0.30-1.21) in rural settings. There was little evidence of an association with diversity of origin. This nationwide cohort study of the association between CL and population growth, in-migration and diversity of origin provides little support for the population mixing hypothesis

Neighbourhood child population density as a proxy measure for exposure to respiratory infections in the first year of life: A validation study.

BACKGROUND:Assessing exposure to infections in early childhood is of interest in many epidemiological investigations. Because exposure to infections is difficult to measure directly, epidemiological studies have used surrogate measures available from routine data such as birth order and population density. However, the association between population density and exposure to infections is unclear. We assessed whether neighbourhood child population density is associated with respiratory infections in infants. METHODS:With the Basel-Bern lung infant development study (BILD), a prospective Swiss cohort study of healthy neonates, respiratory symptoms and infections were assessed by weekly telephone interviews with the mother throughout the first year of life. Using population census data, we calculated neighbourhood child density as the number of children < 16 years of age living within a 250 m radius around the residence of each child. We used negative binomial regression models to assess associations between neighbourhood child density and the number of weeks with respiratory infections and adjusted for potential confounders including the number of older siblings, day-care attendance and duration of breastfeeding. We investigated possible interactions between neighbourhood child population density and older siblings assuming that older siblings mix with other children in the neighbourhood. RESULTS:The analyses included 487 infants. We found no evidence of an association between quintiles of neighbourhood child density and number of respiratory symptoms (p = 0.59, incidence rate ratios comparing highest to lowest quintile: 1.15, 95%-confidence interval: 0.90-1.47). There was no evidence of interaction with older siblings (p = 0.44). Results were similar in crude and in fully adjusted models. CONCLUSIONS:Our study suggests that in Switzerland neighbourhood child density is a poor proxy for exposure to infections in infancy

Frequency of individual CL clusters by cluster size in the empirical and 999 Monte Carlo samples.

<p>Frequency of individual CL clusters by cluster size in the empirical and 999 Monte Carlo samples.</p

Follow-up care of adolescent survivors of childhood cancer: The role of health beliefs

BACKGROUND Little is known about follow-up care attendance of adolescent survivors of childhood cancer, and which factors foster or hinder attendance. Attending follow-up care is especially important for adolescent survivors to allow for a successful transition into adult care. We aimed to (i) describe the proportion of adolescent survivors attending follow-up care; (ii) describe adolescents' health beliefs; and (iii) identify the association of health beliefs, demographic, and medical factors with follow-up care attendance. PROCEDURE Of 696 contacted adolescent survivors diagnosed with cancer at ≤16 years of age, ≥5 years after diagnosis, and aged 16-21 years at study, 465 (66.8%) completed the Swiss Childhood Cancer Survivor Study questionnaire. We assessed follow-up care attendance and health beliefs, and extracted demographic and medical information from the Swiss Childhood Cancer Registry. Cross-sectional data were analyzed using descriptive statistics and logistic regression models. RESULTS Overall, 56% of survivors reported attending follow-up care. Most survivors (80%) rated their susceptibility for late effects as low and believed that follow-up care may detect and prevent late effects (92%). Few (13%) believed that follow-up care is not necessary. Two health beliefs were associated with follow-up care attendance (perceived benefits: odds ratio [OR]: 1.56; 95% confidence interval [CI]: 1.07-2.27; perceived barriers: OR: 0.70; 95%CI: 0.50-1.00). CONCLUSIONS We show that health beliefs are associated with actual follow-up care attendance of adolescent survivors of childhood cancer. A successful model of health promotion in adolescent survivors should, therefore, highlight the benefits and address the barriers to keep adolescent survivors in follow-up care. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc